To resist or limit invasion by pathogens, the human host uses a number of physical and chemical barriers. The microbiota, indigenous microbes living in and on our bodies add an additional and often underappreciated level of protection. We will take advantage of the laboratory protocols, databases, and computational methods developed by the Human Microbiome Project to test hypotheses regarding the role of bacterial community structure in the human oropharynx in resisting invasion by viruses that cause respiratory illness, and bacteria that cause otitis media and pneumonia. We will do so using data collected from an established prospective household study of influenza risk in Nicaragua, the Household Influenza Transmission study. The overall goal of this study is to explore the role of the type and abundance of bacterial species present in the oropharynx (which we will refer to as community structure) and presence of other virus in resisting invasion by influenza virus, and in mediating growth of bacterial species that commonly cause pneumonia and otitis media. Our aim is to apply epidemiologic methods and state of the art genetic sequencing to test the following hypotheses: Hypothesis 1: Influenza infection perturbs the bacterial community structure found in the oropharynx. The extent of perturbation varies by influenza type, the bacterial community structure, and presence of other virus. Hypothesis 2: The changes in bacterial community structure of the oropharynx microbiota in response to influenza infection are a marker of susceptibility to and overgrowth of Streptococcus pneumoniae. Hypothesis 3: The bacterial community structure and presence of commensal virus in the oropharynx microbiota mediates risk of influenza infection. The results of this highly interdisciplinary and innovative molecular epidemiologic study will inform the development of novel strategies to prevent otitis media and bacterial pneumonia and to enhance therapy by manipulating the oropharynx microbiota.